| 1. |
- Anand-Ivell, Ravinder, et al.
(författare)
-
Amniotic fluid INSL3 measured during the critical time window in human pregnancy relates to cryptorchidism, hypospadias, and phthalate load : A large case-control study
- 2018
-
Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9:APR
-
Tidskriftsartikel (refereegranskat)abstract
- The period of the first to second trimester transition in human pregnancy represents a sensitive window for fetal organogenesis, particularly in regard to the development of the male reproductive system. This is a time of relative analytical inaccessibility. We have used a large national biobank of amniotic fluid samples collected at routine amniocentesis to determine the impacts of exogenous endocrine disruptor load on specific fetal biomarkers at this critical time. While adrenal and testicular steroids are highly correlated, they are also mostly positively influenced by increasing phthalate load, represented by the metabolites 7cx-MMeHP and 5cx-MEPP, by perfluorooctane sulfonate (PFOS) exposure, and by smoking, suggesting an adrenal stress response. In contrast, the testis specific biomarkers insulin-like peptide 3 (INSL3) and androstenedione are negatively impacted by the phthalate endocrine disruptors. Using a case-control design, we show that cryptorchidism and hypospadias are both significantly associated with increased amniotic concentration of INSL3 during gestational weeks 13-16, and some, though not all steroid biomarkers. Cases are also linked to a specifically increased variance in the Leydig cell biomarker INSL3 compared to controls, an effect exacerbated by maternal smoking. No influence of phthalate metabolites or PFOS was evident on the distribution of cases and controls. Considering that several animal and human studies have shown a negative impact of phthalate load on fetal and cord blood INSL3, respectively, the present results suggest that such endocrine disruptors may rather be altering the relative dynamics of testicular development and consequent hormone production, leading to a desynchronization of tissue organization during fetal development. Being born small for gestational age appears not to impact on the testicular biomarker INSL3 in second trimester amniotic fluid.
|
|
| 2. |
|
|
| 3. |
- Høyer, Birgit Bjerre, et al.
(författare)
-
Impact of Di-2-Ethylhexyl Phthalate Metabolites on Male Reproductive Function : a Systematic Review of Human Evidence
- 2018
-
Ingår i: Current Environmental Health Reports. - : Springer Science and Business Media LLC. - 2196-5412. ; 5:1, s. 20-33
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: The purpose of this review is to systematically review the literature linking di-2-ethylhexyl phthalate (DEHP) exposure with effects on reproductive health in adult males. RECENT FINDINGS: Thirty-three papers were included of which 28 were cross-sectional. Twenty-one papers investigated semen samples, 18 investigated reproductive hormones, and three studies investigated time to pregnancy. Studies revealed some but inconsistent indications that higher urinary DEHP metabolite levels are associated with an increase in the proportion of spermatozoa with damaged DNA and to a decrease in sperm concentration and motility. A negative association between DEHP metabolites and testosterone levels was more consistent. DEHP metabolites do not seem to be associated with a delay in time to pregnancy, but data are sparse. The studies on DEHP exposure and reproductive biomarkers in men converge to support the hypothesis that DEHP exposure is related to impaired male reproductive function. Longitudinal studies are needed to establish if the observed associations are causal.
|
|
| 4. |
- Juhlin, Tord, et al.
(författare)
-
Renal effects of aspirin are clearly dose-dependent and are of clinical importance from a dose of 160 mg.
- 2008
-
Ingår i: European Journal of Heart Failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 10:9, s. 892-898
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: High doses of aspirin counteract the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors. It is not known how low-dose aspirin, with concomitant ACE-inhibitor treatment, affects renal function. AIM: To study renal effects of different doses of aspirin in elderly healthy volunteers who had an activated renin-angiotensin system. METHODS: Sixteen subjects each received two different doses of aspirin (0 and160 mg or 80 and 320 mg) after pre-treatment with bendroflumethiazide and enalapril, in a randomised double-blind, cross-over fashion. RESULTS: Least square means of the observations 30 to 180 min after dosing, showed that urine flow, GFR, excretion rates of sodium, osmolality clearance and free water clearance were significantly decreased in a dose-dependent manner. Urine flow, sodium excretion rate and free water clearance were significantly lower with 320 mg aspirin vs. 0 mg and 80 mg, and GFR was significantly lower with 320 mg vs. 80 mg. Urine flow, sodium excretion rate, free water and osmolality clearance was significantly lower with aspirin 160 mg vs. 0 mg. CONCLUSION: The dose-dependent renal effects of aspirin are of clinical importance from a dose of 160 mg. The adverse influence of aspirin doses higher than 80 mg should be taken into consideration in patients with heart failure.
|
|
| 5. |
- Jørgensen, Kristian T., et al.
(författare)
-
Perfluoroalkyl substances and time to pregnancy in couples from Greenland, Poland and Ukraine
- 2014
-
Ingår i: Environmental Health: A Global Access Science Source. - 1476-069X. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Perfluoroalkyl substances (PFAS) are suggested to affect human fecundity through longer time to pregnancy (TTP). We studied the relationship between four abundant PFAS and TTP in pregnant women from Greenland, Poland and Ukraine representing varying PFAS exposures and pregnancy planning behaviors. Methods: We measured serum levels of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) in 938 women from Greenland (448 women), Poland (203 women) and Ukraine (287 women). PFAS exposure was assessed on a continuous logarithm transformed scale and in country-specific tertiles. We used Cox discrete-time models and logistic regression to estimate fecundability ratios (FRs) and infertility (TTP >13 months) odds ratios (ORs), respectively, and 95% confidence intervals (CI) according to PFAS levels. Adjusted analyses of the association between PFAS and TTP were done for each study population and in a pooled sample. Results: Higher PFNA levels were associated with longer TTP in the pooled sample (log-scale FR∈=∈0.80; 95% CI 0.69-0.94) and specifically in women from Greenland (log-scale FR∈=∈0.72; 95% CI 0.58-0.89). ORs for infertility were also increased in the pooled sample (log-scale OR∈=∈1.53; 95% CI 1.08-2.15) and in women from Greenland (log-scale OR∈=∈1.97; 95% CI 1.22-3.19). However, in a sensitivity analysis of primiparous women these associations could not be replicated. Associations with PFNA were weaker for women from Poland and Ukraine. PFOS, PFOA and PFHxS were not consistently associated with TTP. Conclusions: Findings do not provide consistent evidence that environmental exposure to PFAS is impairing female fecundity by delaying time taken to conceive.
|
|
| 6. |
- Lenters, Virissa, et al.
(författare)
-
Prenatal phthalate, perfluoroalkyl acid, and organochlorine exposures and term birth weight in three birth cohorts : Multi-pollutant models based on elastic net regression
- 2016
-
Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 124:3, s. 365-372
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Some legacy and emerging environmental contaminants are suspected risk factors for intrauterine growth restriction. However, the evidence is equivocal, in part due to difficulties in disentangling the effects of mixtures. Objectives: We assessed associations between multiple correlated biomarkers of environmental exposure and birth weight. Methods: We evaluated a cohort of 1,250 term (≥ 37 weeks gestation) singleton infants, born to 513 mothers from Greenland, 180 from Poland, and 557 from Ukraine, who were recruited during antenatal care visits in 2002‒2004. Secondary metabolites of diethylhexyl and diisononyl phthalates (DEHP, DiNP), eight perfluoroalkyl acids, and organochlorines (PCB-153 and p,p´‑DDE) were quantifiable in 72‒100% of maternal serum samples. We assessed associations between exposures and term birth weight, adjusting for co-exposures and covariates, including prepregnancy body mass index. To identify independent associations, we applied the elastic net penalty to linear regression models. Results: Two phthalate metabolites (MEHHP, MOiNP), perfluorooctanoic acid (PFOA), and p,p´-DDE were most consistently predictive of term birth weight based on elastic net penalty regression. In an adjusted, unpenalized regression model of the four exposures, 2-SD increases in natural log–transformed MEHHP, PFOA, and p,p´-DDE were associated with lower birth weight: –87 g (95% CI: –137, –340 per 1.70 ng/mL), –43 g (95% CI: –108, 23 per 1.18 ng/mL), and –135 g (95% CI: –192, –78 per 1.82 ng/g lipid), respectively; and MOiNP was associated with higher birth weight (46 g; 95% CI: –5, 97 per 2.22 ng/mL). Conclusions: This study suggests that several of the environmental contaminants, belonging to three chemical classes, may be independently associated with impaired fetal growth. These results warrant follow-up in other cohorts.
|
|
| 7. |
- Rosenquist, Aske Hess, et al.
(författare)
-
Prenatal and postnatal PCB-153 and p,p′ -DDE exposures and behavior scores at 5–9 years of age among children in Greenland and Ukraine
- 2017
-
Ingår i: Environmental Health Perspectives. - 0091-6765. ; 125:10
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Studies have reported some evidence of adverse effects of organochlorine exposures on child development, but the results have been inconsistent, and few studies have evaluated associations with child behavior. OBJECTIVE: We investigated the association between prenatal and early-life exposures to 2,2′,4,4′,5,5′ -hexachlorobiphenyl (PCB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p′ -DDE) and behaviors in children between 5 and 9 y of age. METHODS: In the Biopersistent organochlorines in diet and human fertility: Epidemiologic studies of time to pregnancy and semen quality in Inuit and European populations (INUENDO) cohort, consisting of mother–child pairs from Greenland and Ukraine (n = 1,018), maternal serum PCB-153 and p,p′ -DDE concentrations were measured during pregnancy, and cumulative postnatal exposures during the first 12 months after delivery were estimated using a pharmacokinetic model. Parents completed the Strengths and Difficulties Questionnaire (SDQ), and children’s behaviors were dichotomized as abnormal (high) versus normal/borderline for five SDQ subscales and the total difficulties score. RESULTS: The total difficulties score, an overall measure of abnormal behavior, was not clearly associated with pre- or postnatal exposures to PCB-153 or to p,p′ -DDE. However, pooled adjusted odds ratios (ORs) for high conduct problem scores with a doubling of exposure were 1.19 (95% CI: 0.99, 1.42) and 1.16 (95% CI: 0.96, 1.41) for pre- and postnatal PCB-153, respectively, and 1.25 (95% CI: 1.04, 1.51) and 1.24 (95% CI: 1.01, 1.51) for pre-and postnatal p,p′ -DDE, respectively. Corresponding ORs for high hyperactivity scores were 1.24 (95% CI: 0.94, 1.62) and 1.08 (95% CI: 0.81, 1.45) for pre- and postnatal PCB-153, respectively, and 1.43 (95% CI: 1.06, 1.92) and 1.27 (95% CI: 0.93, 1.73) for pre- and postnatal p,p′ -DDE, respectively. CONCLUSION: Prenatal and early postnatal exposures to p,p′ -DDE and PCB-153 were associated with a higher prevalence of abnormal scores for conduct and hyperactivity at 5–9 y of age in our study population. These findings provide further support for the importance of minimizing organochlorine exposures to young children and to women of childbearing age.
|
|
| 8. |
- Shu, Huan, et al.
(författare)
-
Description of 1st trimester urinary levels of phthalate and phenol metabolites in 2,356 Swedish women in the SELMA study
- 2013
-
Ingår i: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Science. - 0091-6765 .- 1552-9924. ; 121:S1
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Epidemiological studies have found the general population has been exposed to endocrine disrupting chemicals (EDCs) such as phthalates and phenols on a regular basis. Exposures to the developing fetus during critical points in the development are a concern. In the SELMA study we investigate the importance of pre and post natal exposure for EDCs and life style factors for development of chronic diseases in offspring such as asthma and allergy, reproductive related effects, neurodevelopmental disorders and metabolic effects including overweigh and obesity among small children in Sweden. OBJECTIVES: To evaluate the extent of exposure to phthalates and phenols in the urine of 2,356 SELMA pregnant women. METHODS: One spot urine sample was taken during the 1st trimester (wk 10) from 2,356 pregnant (mean age=30), the first visit at the midwifery clinic in Sweden. The samples were analyzed for 10 phthalate metabolites from six different phthalates, bisphenol A and triclosan. Urine was added with isotopically labeled internal standards, digested by glucoronidase and then analyzed by liquid chromatography tandem mass spectrometry without any further purification. The limits of detection (LODs) were between 0.01 and 0.1ng/ml and the coefficients of variation of the quality control samples generally better than 10%. RESULTS: All samples were above the LOD. The geometric mean and range of urinary concentration (ng/ml) was: MEP (68.39; [1.30-4419.35]), MBP (69.42; [3.03-2718.94]), MBzP (16.85; [0.25-3544.51]), MEHP (3.85; [0.14-213.09]), 5-oh (16.59; [0.24-1012.98]), 5-oxo (11.26; [0.05-611.77]), 5-cx (16.07; [0.73-757.17]), 7-oh (6.42; [0.06-1726.48]), 7-oxo (GM=2.98; [0.05-635.49]), 7-cx (10.03; [0.33-1661.24]), BPA (1.54; [0.05-111.26]), and Triclosan (1.25; [0.00-3356.79]). CONCLUSIONS: Exposure of phthalates and phenols are prevalent in Swedish pregnant women (highly susceptible population). Sources of exposure, uptake routes and health effects in children that associated with prenatal exposures will be investigated in the SELMA study.
|
|
| 9. |
- Shu, Huan, 1980-, et al.
(författare)
-
Prenatal phthalate exposure was associated with croup in Swedish infants
- 2018
-
Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 107:6, s. 1011-1019
-
Tidskriftsartikel (refereegranskat)abstract
- AIM: This study examined whether prenatal phthalate exposure was associated with lower or upper airway inflammation in infants.METHODS: From 2007-2010 we used liquid chromatography tandem mass spectrometry, adjusted for creatinine, to analyse 14 phthalate metabolites and one phthalate replacement in the urine of 1,062 Swedish mothers at a median of 10 weeks of pregnancy. This was used to determine any associations between prenatal phthalate exposure and croup, wheezing or otitis in their offspring until 12 months of age, using logistic regression, adjusted for potential confounders.RESULTS: There were significant associations between phthalate metabolites of butyl-benzyl phthalate (BBzP) and di-ethyl-hexyl phthalate (DEHP) concentrations in maternal prenatal urine and croup in 1,062 infants during the first year of life, when adjusted for potential confounders. A dose response relationship was found between prenatal phthalates exposure and maternal reported croup in the children, with a significant association in boys. There was no clear indication with regard to associations between prenatal phthalate exposure and wheezing or otitis media in the children during the first year of life.CONCLUSION: Our analysis suggests that exposure to BBzP and DEHP phthalates was associated with maternal reports of croup in infants up to 12 months of age.
|
|
| 10. |
- Shu, Huan, 1980-, et al.
(författare)
-
PVC flooring at home and uptake of phthalates in pregnant women
- 2019
-
Ingår i: Indoor Air. - : John Wiley & Sons. - 0905-6947 .- 1600-0668. ; 29:1, s. 43-54
-
Tidskriftsartikel (refereegranskat)abstract
- Phthalates are used as plasticizers in polyvinyl chloride (PVC) materials and it is known that phthalates may migrate into the surrounding environment and then become a source for human uptake. The aim of the study was to investigate whether residential PVC flooring was related to the urinary levels of phthalate metabolites determined in pregnant women. The data were from the Swedish SELMA study where sampling was conducted during the time period 2007-2010. Spot urine samples from 1674 women at the end of the first trimester were analyzed for 14 metabolites from seven phthalates and one phthalate alternative. Data on flooring material in the kitchen and the parents' bedrooms as well as potential confounders were collected by postal questionnaires at the same time as the urine samples were taken. Multiple regression modeling by least square geometric mean and weighted quantile sum regression was applied to log-transformed and creatinine-adjusted phthalate metabolite concentrations adjusted for potential confounders from questionnaire data. This study has found significantly higher urinary levels of the BBzP metabolite (MBzP) in pregnant women living in homes with PVC flooring as compared to homes with other flooring materials
|
|
| 11. |
- Shu, Huan, 1980-, et al.
(författare)
-
Temporal Trends of Phthalate Exposures during 2007-2010 in Swedish Pregnant Women
- 2018
-
Ingår i: Journal of Exposure Science and Environmental Epidemiology. - : Nature Publishing Group. - 1559-0631 .- 1559-064X. ; 28, s. 437-447
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The general population is exposed to phthalates, a group of chemicals with strong evidence for endocrine disrupting properties, commonly used in a large number of consumer products. Based on published research and evidence compiled by environmental agencies, certain phthalate applications and products have become restricted, leading to an increasing number of “new generation compounds” coming onto the market during recent years replacing older phthalates. Some examples of such newer compounds are di-iso-nonyl phthalate (DiNP), di-iso-decyl phthalate (DiDP), and most recently di-isononyl-cyclohexane-1,2-dicarboxylate (DiNCH).Objectives: In order to evaluate temporal trends in phthalate exposure, first trimester urinary biomarkers of phthalates were measured in the Swedish SELMA study over a period of 2.5 years (2007–2010).Methods: We collected first morning void urine samples around week 10 of pregnancy from 1651 pregnant women. Spot samples were analyzed for 13 phthalate metabolites and one phthalate replacement and least square geometric mean (LSGM) levels of the metabolites were compared between the sampling years when adjusted for potential confounders.Results: All 14 metabolites were detectable in more than 99% of the SELMA subjects. The levels were generally comparable to other studies, but the SELMA subjects showed slightly higher exposure to butyl-benzyl phthalate (BBzP) and di-butyl phthalate (DBP). Di-ethyl-hexyl phthalate (DEHP) metabolites levels decreased while DiNP, DiDP/di-2-propylheptyl phthalate (DPHP), and DiNCH metabolites levels increased during the sampling period.Conclusions: Urinary metabolite levels of the older phthalates and more recently introduced phthalate replacement compound changed during the short sampling period in this Swedish pregnancy cohort. Our results indicate that replacement of phthalates can make an impact on human exposure to these chemicals. During this particularly vulnerable stage of life, phthalate exposures are of particular concern as the impacts, though not immediately noticeable, may increase the risk for health effects later in life.
|
|
| 12. |
- Thomsen, Anne Marie L., et al.
(författare)
-
Female exposure to phthalates and time to pregnancy : A first pregnancy planner study
- 2017
-
Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 32:1, s. 232-238
-
Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION Is female exposure to phthalate metabolites associated with reduced fecundity, as estimated by prolonged time to pregnancy (TTP)? SUMMARY ANSWER Female exposure to monoethyl phthalate (MEP) but not monobutyl phthalate (MBP), monobenzyl phthalate (MBzP) and monoethylhexyl phthalate (MEHP) was associated with a longer TTP. WHAT IS KNOWN ALREADY Male exposure to phthalates is potentially associated with adverse effects on human fecundity in epidemiological studies, but little is known about the potential effects on female reproduction. STUDY DESIGN SIZE AND DURATION A cohort study with prospective data based on 229 women from a Danish cohort of 430 first pregnancy planning couples enrolled in 1992-1994. In 2009, urinary analyses of phthalate metabolites were performed on stored urine samples from this cohort. PARTICIPANTS/MATERIALS, SETTING AND METHODS We analyzed MEP, MBP, MBzP and MEHP in female morning spot urine samples collected daily during the first 10 days of menstrual cycles after discontinuation of contraception. The exposure assessment was based on the mean of two measurements from each woman collected in a period of 6 menstrual cycles. We used Cox regression with discrete time to estimate fecundability ratios (FRs) and 95% CI in relation to the average urine metabolite concentration exposure level, controlled for age and BMI, and the time-varying variables smoking and alcohol. MAIN RESULT AND ROLE OF CHANCE Urinary concentration of MEP was associated with a decreased fecundity (adjusted FR 0.79; 95% CI: 0.63; 0.99) corresponding to a 21% decreased probability of conception for each natural log (ln) unit increase in MEP. No significant association with TTP was found for MBP, MBzP and MEHP. LIMITATIONS REASONS FOR CAUTION Subfertile women were overrepresented in the study population due to exclusion of 77 high fertile women who became pregnant in the first cycle when urine collection began. WIDER IMPLICATIONS OF THE FINDINGS Our results suggest that female exposure to MEP may have an adverse effect on female fecundity, but these findings need to be replicated in a larger and newer cohort study with sufficient exposure contrast if the use of diethyl phthalate (DEP) and thereby MEP in the future potentially should be regulated in cosmetics and industrial consumer products.
|
|
| 13. |
|
|
| 14. |
- Xu, Yiyi, et al.
(författare)
-
Occupational exposure to asphalt mixture during road paving is related to increased mitochondria DNA copy number : A cross-sectional study
- 2018
-
Ingår i: Environmental Health: A Global Access Science Source. - : Springer Science and Business Media LLC. - 1476-069X. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Asphalt workers are exposed to polyaromatic hydrocarbons (PAHs) from hot mix asphalt via both inhalation and dermal absorption. The use of crumb rubber modified (CRM) asphalt may result in higher exposure to PAHs and more adverse effects. Our aim is to assess occupational exposure to PAHs from conventional and CRM asphalt paving by measuring PAH metabolites in urine, and to investigate the effects on mitochondrial DNA copy number (mtDNAcn) and telomere length. Methods: We recruited 116 workers paving conventional asphalt, 51 workers paving CRM asphalt and 100 controls in Sweden, all males. A repeated-measures analysis included 31 workers paving both types of asphalt. Urine and blood samples were collected pre-working on Monday morning and post-working on Thursday afternoon after 4 days working. PAH metabolites: 1-hydroxypyrene (1-OH-PYR) and 2-hydroxyphenanthrene (2-OH-PH) were measured in urine by LC-MS/MS. Relative mtDNAcn and telomere length were measured by quantitative PCR. Results: Conventional and CRM asphalt workers showed higher 1-OH-PYR and 2-OH-PH than controls (p < 0.001 for all). Relative mtDNAcn were 0.21 units (p < 0.001) higher in conventional asphalt workers and 0.13 units (p = 0.010) higher in CRM asphalt workers compared to controls. Relative telomere length did not differ across occupational groups, but it was positively associated with increment of 2-OH-PH (β = 0.075, p = 0.037) in asphalt workers. The repeated-measures analysis showed no difference in either increment of 1-OH-PYP, or changes in effect biomarkers (mtDNAcn or telomere length) between paving with conventional and CRM asphalt. Increment of 2-OH-PH was smaller after paving with CRM asphalt. Conclusions: Road asphalt paving in open areas resulted in PAHs exposure, as shown by elevation of PAH metabolites in urine. Asphalt workers may experience oxidative stress, evidenced by alternation in mtDNAcn; however the effects could not be fully explained by exposure to PAHs from the asphalt mixture.
|
|
